US9751848B2 - Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst - Google Patents

Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst Download PDF

Info

Publication number
US9751848B2
US9751848B2 US15/302,936 US201515302936A US9751848B2 US 9751848 B2 US9751848 B2 US 9751848B2 US 201515302936 A US201515302936 A US 201515302936A US 9751848 B2 US9751848 B2 US 9751848B2
Authority
US
United States
Prior art keywords
catalyst
hydrogenation
reaction
salt
support
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
US15/302,936
Other languages
English (en)
Other versions
US20170029394A1 (en
Inventor
David Dunn
Howard Winston Tyrrell SUTTON
John Ing Chuan DALY
Simon Jonathon Grant
Lian HUTCHINGS
Patrice Georges Antonin RIBIERE
Matthew Richard GIBBINGS
Sergio Aaron GAMBOA MARTINEZ
Craig Anderson
Yulia ROGAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Thomas Swan and Co Ltd
Original Assignee
Thomas Swan and Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Thomas Swan and Co Ltd filed Critical Thomas Swan and Co Ltd
Assigned to THOMAS SWAN & CO. LTD reassignment THOMAS SWAN & CO. LTD ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GAMBOA MARTINEZ, Sergio Aaron, ANDERSON, CRAIG, DALY, John Ing Chuan, DUNN, DAVID, GIBBINGS, Matthew Richard, GRANT, SIMON JONATHON, HUTCHINGS, Lian, RIBIERE, Patrice Georges Antonin, ROGAN, Yulia, SUTTON, Howard Winston Tyrrell
Publication of US20170029394A1 publication Critical patent/US20170029394A1/en
Application granted granted Critical
Publication of US9751848B2 publication Critical patent/US9751848B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/06—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/58—Platinum group metals with alkali- or alkaline earth metals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B31/00—Reduction in general
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses

Definitions

  • the present invention relates to stereoselective hydrogenation and in particular to the diastereoselective hydrogenation of bicyclic alkenes using known and novel hydrogenation catalysts.
  • Heterogeneous hydrogenation of alkenes is a well-established technique.
  • the mechanism of action of a metal catalyst supported on an inert solid is generally considered to occur through the absorption of hydrogen onto the catalyst metal surface and the subsequent approach of the carbon-carbon double bond to that surface giving rise to hydrogen addition across one side of the double bond.
  • the planar structure of the alkene is transformed into the well-known tetragonal carbon structure, which may give rise to a particular set of chiral centre(s) depending upon the structure of the parent alkene.
  • Metals used as catalyst are typically nickel, palladium, platinum or other precious metals (platinum group metals).
  • the newly formed chiral centre will generate a mixture of diastereoisomers.
  • the mixture of diastereoisomers is expected to be a 50/50 mixture.
  • a functional group on an unsaturated (i.e. alkene) substrate bearing, or not, existing chirality will have an asymmetric inductive effect, resulting in the preferential formation of one diastereoisomer over the another.
  • Hoveyda et al. describe several examples of directed heterogeneous hydrogenations where a functional group interacts with the metal surface of the catalyst, favouring the approach of the substrate to the catalyst by a specific side, and leading to the delivery of hydrogen to the unsaturation site in a syn fashion (with respect to the directing group). That disclosure provides that “the nature of the directing group, solvent, catalyst, support, and hydrogen pressure” influence the product.
  • 1,3-induction often requires the use of a chelating agent.
  • either the reaction centre and the chiral centre are tethered together and the reagent is delivered externally of the chelate or the reagent becomes part of the chelate itself.
  • Most reactions described are limited to nucleophilic additions, including carbonyl reductions with a metal hydride where the carbonyl and the ⁇ -chiral centre with an alcohol or ether functional group are first complexed with a Lewis acid.
  • FIG. 1 shows use of magnesium Bromide as a complexing agent to achieve Pd-catalysed diastereoselective hydrogenation as shown in Organic Letters, 2002, 1347-1350 by A Bouzide.
  • the chiral centre responsible for the diastereomeric induction can be pre-existing to the hydrogenation reaction (and its configuration predetermined, as in all three above papers), it could also be formed in situ prior to the final reduction (e.g. when hydrogenating dienes). In the latter case the first (favoured) reduction to take place will provide a racemic mixture of a partially reduced intermediate, but the newly formed chiral centre could influence the formation of the second (final) one, resulting in a diastereoselective reaction.
  • a meso isomer is a non-optically active member of a set of stereoisomers, wherein at least two of the stereoisomers are optically active.
  • the meso isomer whilst containing two or more chiral centres the meso isomer is itself not chiral.
  • a meso compound structure is superposable on its mirror image i.e. all aspects of the objects coincide and a meso isomer it does not produce a “(+)” or “( ⁇ )” reading in polarimetry.
  • transition metal catalysts such as nickel, palladium or platinum on readily available supports such as charcoal, which may use simple and readily available adjuncts or auxiliaries to prove stereoselective hydrogenation an industrial scale.
  • desired catalysts should allow the use of a simple experimental methodology (e.g. a one-pot reaction), with a simple work up (e.g. by simple filtration) such as to remove catalyst and auxiliaries from reaction product.
  • the present invention is directed to a means of selective hydrogenation for disturbing the balance away from a statistical mix of diastereoisomers produced in hydrogenation of alkene using a metal cataltyst.
  • US 2013/0165697 application describes the use of alkali doped Pd/C catalyst(s) to selectively reduce phenol compounds to the corresponding ketones products, in good yield when using their solution in an alcohol solvent.
  • All 17 examples described the use of a broad range of weakly basic alkali salts (either lithium, sodium, potassium as cation, and carbonate or acetate as anion). All these various salts can influence the reaction pathway, i.e. limit the formation of side-products and over-reduction to the cyclohexanol derivatives to provide a good yield of the ketone products. But none these alkali doping agents demonstrate any stereocontrol on the considered reaction nor is any particular pattern in their effectivity evident.
  • diastereoselective hydrogenation of a specific substrate is provided.
  • the hydrogenation is mediated by a catalyst supported on a substrate and in conjunction with an auxiliary catalytic component also termed herein the Salt.
  • an auxiliary catalytic component also termed herein the Salt.
  • Cycl represent a cyclic moiety and R 1 represents H or a further organic chemical moiety and wherein hydrogenation of the alkene provides a meso isomer.
  • Cycl represents an unsaturated moiety being a five or six membered heterocyclic ring, wherein the heteroatom is one of O, S, N or P.
  • the heteroatom is preferably O.
  • Cycl is preferably selected from furan (C 4 H 3 O—), 4H-pyran (C 5 H 6 O—) ring moiety. Cycl is still more preferably furan and yet more preferably linked at the 2 position (i.e. adjacent the oxygen).
  • the most preferred substrate is 2,2′-di(2-tetrahydrofuryl)propane, also known as 2,2-difurylpropane.
  • R 1 preferably represents an organic chemical moiety of molecular weight less than 500 Da, preferably less than 128 Da, this limit reduces and in the latter case avoids unduly bulky groups which may inhibit interaction with the catalyst surface.
  • R 1 represents H or an achiral organic chemical group, preferably an alkyl chain.
  • the alkyl chain may be optionally substituted with O, S, N or P based functionality but this is not preferred as it may influence catalysts selectivity.
  • R 1 represents H or a C 1 to C 6 alkyl chain, optionally but not preferably, substituted with O, S, N or P based functionality.
  • R 1 represents H or a C 1 to C 6 alkyl chain it is speculated that the primary interaction with the catalytic composition of the invention (i.e. the combination of catalyst, substrate and Salt) is optimised to give the highest stereo selectivity.
  • the most preferred R 1 is H or CH 3 , this is thought to arise due to its low stereochemical bulk enabling optimum interaction between the catalytic composition.
  • formula 1 may comprise any combination of the moieties mentioned in the previous paragraphs a preferred combination is wherein Cycl provides alpha, beta unsaturation to the double bond and R 1 represents a C 1 to C 6 alkyl chain.
  • 1,3-induction via a chelate with lithium salts at a catalyst/substrate surface is thought to be involved.
  • the compound may be thought of as a compound that provides two prochiral Csp2 centres on separate unsaturations and not part of the same ring.
  • the catalyst component of the catalyst composition in the present invention is a metal, and specifically a metal hydrogenation catalyst, which is preferably selected from platinum, palladium, rhodium, ruthenium and nickel, more preferably selected from platinum, palladium, rhodium and ruthenium in providing higher selectivity.
  • the metal catalyst is preferably palladium. Palladium provides the highest stereochemical selectivity in the catalyst composition in the present invention.
  • the metal catalyst whilst normally an preferably provided as the pure metal may be provided as in other oxidation state known to be effective for hydrogenation catalysis.
  • a precursor such as a metal oxide for subsequent reduction such as to provide in situ metal may be used, an example being palladium oxide.
  • the catalyst component preferably comprises no more than a trace, less than 100 ppm, preferably less than 10 ppm, of non-catalyst metal.
  • the catalyst preferably comprises no more than a trace, less than 100 pmm, preferably less than 10 ppm, of other anions ions besides chloride bromide or carbonate. Ppm herein is ppm by weight (mg/kg).
  • the catalyst, a hydrogenation catalyst, of the present invention is supported upon a Support in conjunction with the Salt to provide the catalyst composition in the invention.
  • the support is a solid.
  • the support may be any inert support catalyst carrier known to be suitable as a support for the catalyst of the present invention.
  • Preferred supports are carbon, alumina, silica, titanium dioxide, calcium carbonate, lithium aluminate and barium sulphate. More preferred supports are carbon (such as in the form of charcoal), silica and alumina. If the preferred support is carbon, more preferred is amorphous carbon and most preferred the support is charcoal. The most stereoselective support is Alumina. Results have shown that the specific form of palladium on charcoal, as reflected in comparison of supports from different suppliers has a minimal effect on stereoselectivity of hydrogenation. This effect is in the order of 6% by weight in stereoisomer product, this against a repeatability of around 2% by weight stereoisomer product between repeat experiments under nominally identical conditions.
  • the support preferably has a surface area of from 10 to 1500 m 2 /g, preferably from 500 to 1500 m 2 /g, most preferably from 1000 to 1500 m 2 /g.
  • the Support is preferably provided in a particulate form with a particle size below 1 mm, the support is more preferably of particle size between 1 and 100 ⁇ m, as measured using light scattering using a Malvern mastersizer (Tm) by the D 4,3 measure.
  • Tm Malvern mastersizer
  • Catalysts of the type suitable for use in the present invention in conjunction with the support may be provided with an inert coating to facilitate storage. Whilst this material is preferentially removed prior to use such material has in practice shown negligible effect on catalyst performance.
  • the catalyst on the substrate is preferably provided in a liquid reaction mixture, most preferably as a slurry, this appears to provide a maximum reaction rate.
  • an immobilised support washed over by reaction medium in liquid or gaseous form is also a possibility.
  • the catalyst in conjunction with the support used in the present invention is for the catalysis of hydrogenation using hydrogen gas.
  • hydrogenation is well known to the skilled person in the art in the hydrogen gas is provided under pressure in a sealed container, preferably with agitation, in a conventional manner.
  • the hydrogen used is 99.9% pure or better.
  • the Salt (Auxiliary Catalytic Component)
  • salts are known in conjunction with supported hydrogenation catalysts to influence reaction products for hydrogenating a substrate the use of such salts to alter the stereochemistry of the reaction products is not known.
  • the mechanism by which such salts influence reaction mechanism is a matter of speculation and experimental investigation has provided several surprising and unpredicted influences of salt type.
  • the Salt of the present invention may also act as the support for the catalyst.
  • each of the catalyst, the support and the Salt may contribute to selectivity and therefore a combination of the three features as separate materials is preferred, i.e., wherein each of the catalyst, support and Salt are chemically different materials (whether or not they are physically aggregated).
  • the salt is a lithium salt.
  • the lithium salt may be an organo- carboxylate, an organo-sulphate, and aluminate, chloride, bromide, carbonate, hydroxide or borate.
  • the salts may be hydrated salts.
  • the lithium salt is preferably a metaborate, tetraborate, chloride, bromide, hydroxide, organo- carboxylate (preferably RCO 2 ⁇ ).
  • Preferable carboxylates are the acetate, benzoate, oxalate and palm itate, more preferable carboxylates are the acetate, benzoate and palmitate.
  • a mixture lithium anions may be used.
  • the preferred salts are the metaborate, tetraborate, chloride, hydroxide and benzoate.
  • the preferred salt may be metaborate, tetraborate, giving a high degree of conversion and selectivity.
  • the most preferred lithium salts are the tetraborate, anhydrous metaborate, metaborate monohydrate or dihydrate.
  • the hydroxide has been found in some instances to give rise to undesirable byproducts, thought to be due to its highly alkaline nature.
  • the lithium salt, and the reaction composition as a whole preferably does not comprise any divalent or trivalent metal ions as these appear to reduce selectivity.
  • the catalyst composition and the reaction composition as a whole preferably consists of lithium salt as the only inorganic cation. More preferably the catalyst composition consists of lithium salt as the only inorganic cation.
  • the catalyst composition of the invention comprises the catalyst, the support and the salt.
  • the loading of the catalyst on the support is preferably from 0.25% to 25% by weight, more preferably in the range 1% to 10%, most preferably 2 to 5%.
  • the support itself can influence upon the stereoselectivity of hydrogenation can the catalyst and the salt.
  • high loadings of catalyst on the support (>10%) appear to mask the support with which the salt adjunct is thought to possibly interact and seem to reduce the selectivity effect.
  • the most preferred catalyst loading is therefore in the range 2 to 5% as there is a balance between catalyst, substrate and Salt contributions to selectivity.
  • the combination of catalyst on support is a solid and as mentioned may be in the form of a powder.
  • the powder may be aggregated in the form of a pellets (for example an aggregate of particles forming the unit of dimensions from 1 to 10 mm) or as a pastes, such as a water based paste.
  • the catalyst composition preferably comprises Salt at the level of 1 to 600 mole equivalent with respect to the catalyst, preferably at 5 to 300 mole equivalent with regards to the catalyst, most preferably at 5 to 100 molar equivalents with respect to the catalyst. It been recalled that for the purposes of the definition in the present invention the catalyst is the metal presented on the support rather than the combination of catalyst with support and/or Salt.
  • the present invention requires a combination of the catalyst, the support and the Salt as mentioned above.
  • This combination of materials may be prepared as follows:
  • Loading of catalyst on to support substrate is by known techniques. Loading a catalyst onto the support is preferable prior to any subsequent step in catalyst composition preparation.
  • Combining the catalyst on the support with the Salt may take place during catalyst preparation (for example by co-precipitation or co-impregnation support with catalyst), prior to reaction (for example by pre-mixing or pre-contacting the catalyst on the support with salt as a physical mixture) or immediately prior to reaction (catalyst and salt charged separately at the start of the reaction), i.e. prior to the introduction of hydrogen.
  • Combination of the catalyst on the support with the Salt is most preferably prior to reaction or during reaction or most preferably during reaction (catalyst and salt charged separately at the start of the reaction), this appears to give the most facile reaction condition set up and good selectivity.
  • a liquid solvent is used, preferred solvents are: alkanes and in particular C 4 to C 8 alkanes; aromatic solvents in particular toluene, halogenated solvents in particular dichloromethane; polar non-protic solvents such as ethers in particular methyl tert-butyl ether (MTBE) or tetrahydrofuran (THF); esters, in particular ethyl acetate, and polar protic solvents in particular alcohols (more preferably methanol, isopropanol); or water.
  • alkanes and in particular C 4 to C 8 alkanes aromatic solvents in particular toluene, halogenated solvents in particular dichloromethane
  • polar non-protic solvents such as ethers in particular methyl tert-butyl ether (MTBE) or tetrahydrofuran (THF)
  • esters in particular ethyl acetate, and polar protic solvents in particular alcohols (
  • the preferred solvents are heptane, MTBE, THF, ethyl acetate, methanol, ethanol, n-propanol and isopropanol. Most preferred is isopropanol as this provides the higher selectivity.
  • a solvent When a solvent is used it is preferably used in a quantity equivalent to 5 times or less the volume of the substrate, preferably equivalent to 0 to 2 times the volume of the substrate, most preferably from 0 to 1 times the volume of the substrate.
  • a solvent is preferably used when the substrate is not liquid at the reaction temperature. When the substrate is not liquid at the reaction temperature the solvent is used of a type and a quantity so as to dissolve the substrate at the reaction temperature.
  • a liquid which does not dissolve the substrate is not a solvent for the purposes of the present invention. Water may be used but this is not a solvent for many substrates but may, nevertheless, be used (or be present) as an effective biphasic system can result.
  • the temperature range of the present invention for performing the method and use of the catalyst in the hydrogenation reaction is 10 to 200° C., and preferably between 50° C. and 120° C.
  • the pressure used for performing the method and use of the catalyst in the hydrogenation reaction of the present invention is above 100 kPa, preferably above 200 kPa, most preferably above 500 kPa.
  • the pressure of reaction may be in the range 100 kPa to70 MPa (1 to 700 bar), preferably 200 kPa to 5 MPa (2 to 50 bar), more preferably 500 kPa to 1200 kPa (5 to 12 bar). Higher pressure provides greater selectivity.
  • reaction time of the present invention used for performing the method and use of the catalyst in the hydrogenation reaction is 6 to 48 hours, preferably 6 to 24 hours, most preferably 18 to 24 hours.
  • the reaction time is not understood to influence selectivity but has a greater influence on total reaction conversion of substrate.
  • Reactions of the present invention generally go to completion or near completion and the time ranges indicated when using representative temperatures and pressures particularly with respect to the catalyst used, as known in the art.
  • the present invention has been developed with stirred reactors, but it is understood by the man of the art that such a diastereoselective heterogeneous reaction could be adapted to other plant hydrogenation equipment such as Buss®-loop or jet-loop reactors or flow reactors such as multi-plate reactors (e.g. as some manufactured by Alpha-Laval) as these reactors are known to be able to handle the catalyst slurry and to provide extra temperature and mixing (with impact on mass transfer and reaction rate) controls.
  • plant hydrogenation equipment such as Buss®-loop or jet-loop reactors or flow reactors such as multi-plate reactors (e.g. as some manufactured by Alpha-Laval) as these reactors are known to be able to handle the catalyst slurry and to provide extra temperature and mixing (with impact on mass transfer and reaction rate) controls.
  • the first aspect the present invention is a method of stereoselective hydrogenation, the method comprising providing the substrate, the catalyst, the support and the salt as defined above and carrying out a hydrogenation of the substrate using hydrogen.
  • the preferred reaction conditions being also as mentioned above.
  • the method of the first aspect of the present invention may provide the steps:
  • the use may provide greater than statistical meso isomer hydrogenation product, more preferably greater than 52%, and still more preferably greater than 57% and greater than 70%. This use has been shown to be particularly effective in providing higher diastereoisomer (and particularly meso) hydrogenation product in comparison to statistical i.e. (50/50) and higher than reference (i.e. untreated catalyst) in stereoselective hydrogenation.
  • the third aspect the present invention is a catalyst on a support in combination with the Salt, all as defined above with the limitation that the salt is one or more of lithium metaborate or tetraborate.
  • the present invention is exemplified by the following reaction using the most preferred substrate:
  • 2,2′-di(2-tetrahydrofuryl)propane also known as 2,2-difurylpropane, 2,2′-isopropylidene bis(terahydrofuran), OOPS and DTHFP has several uses including as a polar modifier in butadiene polymerisation. Such uses are disclosed in many documents, including U.S. Pat. No. 5,698,646, W02009/134665 and EP 1462459 and WO2012119917A. The material is used industrially on a large scale and can be produced by means of the above hydrogenation reaction.
  • WO2011/087841 discloses improved utility for the meso isomer of 2,2-di(2-tetrahydrofuryl)propane.
  • no selective synthetic route for production of the meso isomer is available. Production being based upon separation of the statistical stereoisomeric mixture by physical means. This is wasteful of the undesired R,R and S,S isomers.
  • Hydrogenation output routine analysis was carried out by GC-FID using an Agilent 6890 equipment with flame ionisation detection (FID).
  • GC-FID was ran using a RTX-624Sil MS column, hydrogen (constant pressure 5.8 psi) as a carrier gas for GC-FID, an injection at 290° C. (with a split ratio of 10) and the following temperature ramp: 60° C. for 5 min, ramping up at 10° C./min to 320° C., and held for 5 min.
  • the detector temperature was set at 280° C.
  • DTHFP GC profile shows two separated peaks with different close retention times corresponding to the two diastereoisomers. Meso diastereoisomer correspond to the peak with the lowest retention time, the sample being validated by the analysis methods in the previous paragraph.
  • meso ⁇ ⁇ % meso ⁇ ⁇ DTHFP ⁇ ⁇ isomer ⁇ ⁇ ( R , S ⁇ ⁇ or ⁇ ⁇ S , R ) ⁇ ⁇ GC ⁇ ⁇ area ⁇ ⁇ % all ⁇ ⁇ DTHFP ⁇ ⁇ isomers ⁇ ⁇ ( R , S ⁇ ⁇ or ⁇ ⁇ S , R / S , S / R , R ) ⁇ GC ⁇ ⁇ area ⁇ ⁇ %
  • Each reactor has a working volume up to 7 m L, is equipped with an internal glass tube and a paddle stirrer, and can withstand pressures of up to 50 bars.
  • reaction was deemed to start once the target temperature was reached and stabilised. After the 18 hours, the heating was stopped. Once back at room temperature, the pressure was released, the carousel opened and an aliquot of the reaction crude was filtered and analysed as below. Variations in the method are carried out at equal molarity of reactants.
  • the Salt of the present invention is a lithium salt.
  • the product further comprised a 50/50 mixture of the R/R and S/S isomers, this was established in preliminary experiment and has been assumed in the results shown in table 3 onward.
  • the yield in each case was 60% hydrogenation products or above.
  • Low reaction yield (in the order of 60%) on equivalent conditions as relevant to table 3 was evident with lithium chloride and lithium hydroxide, as compared to salts such as the meta and tetraborate at clearly above 60%.
  • Reactions were performed in reaction tubes containing 6 g of material, using DFP [2,2-di(2-furyl)propane] as substrate, a catalyst loading of 0.5 to 2%, powdered lithium salts (5 to 600 mole equivalent vs the metal of the catalyst), solvent at 0 to 2 volumes against substrate, temperatures from 60 to 100° C., and hydrogen pressures from 1000 to 3000 kPa (10 to 30 bar).
  • the method was otherwise as disclosed in more detail for table 1. As such the a variation in % meso isomer product reflects those differences in condition.
  • the catalysts were used at 2 to 5% w/w metal on the named substrate with the exception of Nickel at 22% w/w on silica.
  • the catalyst used was 5% Pd/C 50% wet with a loading of 1 to 2% w/w in regards to the starting material.
  • the salts used at equivalent molar amounts of 5 to 100 equivalents of Li to Pd metal. Pressures from 10 to 30 bar.
  • Substrate and solvents were added afterwards. Other methods of addition were tested such as stirring the reaction mixture for 6 days under room temperature and atmosphere before pressurising the vessel (Stirring reaction mixture); grinding the catalyst and the salt into a mixture of powders (Ground mixture of powders); and creating a suspension of the catalyst and salt using an appropriate solvent which was later dried under vacuum (Dried suspension).
  • the catalyst used was 5% Pd/C 50% wet with a loading of 2% w/w in regards to the starting material.
  • the solvent is IPA at 1 volume against the starting material, unless stated otherwise.
  • the first two entries correspond to reactions carried out in a 1-L Parr reactor at 100 C. and with 10 bar of hydrogen pressure. Other entries correspond to reactions performed in the Baskerville ® carousel described earlier. Temperature for the latter reactions was in the range of 60 to 100 C., and pressure from 6 to 15 bar.
  • the catalyst used was 5% Pd/C 50% wet.
  • the solvent was DCM at 50 volumes for the first two entries of the table and at 1 volume for the last two, against the starting material.
  • the first entry corresponds to the results published by Bouzide; those reactions were performed at room temperature and atmosphere of hydrogen.
  • the remaining entries show the results acquired from using the Baskerville carousel described earlier. Temperature for the latter reactions was 80° C. and hydrogen pressure 15 bar.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)
US15/302,936 2014-09-26 2015-09-28 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst Active US9751848B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1417035.1 2014-09-26
GBGB1417035.1A GB201417035D0 (en) 2014-09-26 2014-09-26 Enantioselective hydrogenation
PCT/GB2015/052802 WO2016046575A1 (en) 2014-09-26 2015-09-28 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2015/052802 A-371-Of-International WO2016046575A1 (en) 2014-09-26 2015-09-28 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/470,691 Continuation US10000460B2 (en) 2014-09-26 2017-03-27 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Publications (2)

Publication Number Publication Date
US20170029394A1 US20170029394A1 (en) 2017-02-02
US9751848B2 true US9751848B2 (en) 2017-09-05

Family

ID=51901190

Family Applications (2)

Application Number Title Priority Date Filing Date
US15/302,936 Active US9751848B2 (en) 2014-09-26 2015-09-28 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst
US15/470,691 Active US10000460B2 (en) 2014-09-26 2017-03-27 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Family Applications After (1)

Application Number Title Priority Date Filing Date
US15/470,691 Active US10000460B2 (en) 2014-09-26 2017-03-27 Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Country Status (5)

Country Link
US (2) US9751848B2 (zh)
EP (1) EP3134203B1 (zh)
CN (1) CN106414419B (zh)
GB (2) GB201417035D0 (zh)
WO (1) WO2016046575A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10000460B2 (en) * 2014-09-26 2018-06-19 Thomas Swan & Co. Ltd Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10358430B2 (en) 2017-08-25 2019-07-23 Thomas Swan & Co. Ltd Oligomeric (TH)FP, production and uses therefor
CN108997266B (zh) * 2018-08-06 2020-06-09 浙江清和新材料科技有限公司 一种2,2-二(2-呋喃基)丙烷加氢制2,2-二(2-四氢呋喃基)丙烷的方法
CN113362905B (zh) * 2021-06-08 2022-07-08 浙江大学 一种基于深度学习的不对称催化反应对映选择性预测方法
CN114669294A (zh) * 2022-04-13 2022-06-28 宏业生物科技股份有限公司 2,2-二(2-呋喃基)丙烷加氢制2,2-二(2-四氢呋喃基)丙烷的复合催化剂
CN116212630B (zh) * 2023-05-06 2023-07-07 北京安吉贝玛健康科技有限公司 一种浓缩型高效除味剂及其制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3784481A (en) * 1970-04-06 1974-01-08 Inst Francais Du Petrole Hydrogenation catalysts containing a transition metal salt and an aluminum hydride compound
US4115462A (en) 1974-06-25 1978-09-19 Bayer Aktiengesellschaft Gas phase aromatic hydrogenation using palladium lithium aluminum spinel catalyst
US4577035A (en) 1984-11-28 1986-03-18 Huffman George W 2,2'-Isopropylidine bis(tetrahydrofuran)
US6015927A (en) 1997-06-30 2000-01-18 Bayer Aktiengesellschaft Process for preparing cyclohexanones by hydrogenation of the corresponding phenols (II)
EP1767520A1 (en) 2005-09-22 2007-03-28 Air Products and Chemicals, Inc. Hydrogenation of aromatic amines to alicyclic amines using a ruthenium catalyst supported on lithium aluminate
CN101502800A (zh) 2008-12-30 2009-08-12 西安凯立化工有限公司 烷基苯酚一步合成烷基环己酮用催化剂及其制备方法
US20130165697A1 (en) 2011-12-24 2013-06-27 Alessa Gmbh Method for Preparing Cyclic Ketones
CN103319308A (zh) 2013-07-08 2013-09-25 濮阳天健生物科技有限公司 一种8(z/e)-十二碳烯-1-醇的合成方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU209875B (en) * 1990-12-21 1994-11-28 Mta Koezponti Kemiai Kutato In Process for production of mannit0l with stereoselective catalytic hydrogenation on raney-copper catalysts
GB201417035D0 (en) * 2014-09-26 2014-11-12 Swan Thomas & Co Ltd Enantioselective hydrogenation

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3784481A (en) * 1970-04-06 1974-01-08 Inst Francais Du Petrole Hydrogenation catalysts containing a transition metal salt and an aluminum hydride compound
US4115462A (en) 1974-06-25 1978-09-19 Bayer Aktiengesellschaft Gas phase aromatic hydrogenation using palladium lithium aluminum spinel catalyst
US4577035A (en) 1984-11-28 1986-03-18 Huffman George W 2,2'-Isopropylidine bis(tetrahydrofuran)
US6015927A (en) 1997-06-30 2000-01-18 Bayer Aktiengesellschaft Process for preparing cyclohexanones by hydrogenation of the corresponding phenols (II)
EP1767520A1 (en) 2005-09-22 2007-03-28 Air Products and Chemicals, Inc. Hydrogenation of aromatic amines to alicyclic amines using a ruthenium catalyst supported on lithium aluminate
CN101502800A (zh) 2008-12-30 2009-08-12 西安凯立化工有限公司 烷基苯酚一步合成烷基环己酮用催化剂及其制备方法
US20130165697A1 (en) 2011-12-24 2013-06-27 Alessa Gmbh Method for Preparing Cyclic Ketones
CN103319308A (zh) 2013-07-08 2013-09-25 濮阳天健生物科技有限公司 一种8(z/e)-十二碳烯-1-醇的合成方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
International Search Report issued in application No. PCT/GB2015/052802 on Dec. 3, 2015.
UK Intellectual Property Office Search Report issued in application No. GB1417035.1 on Mar. 26, 2015.
Written Opinion issued in application No. PCT/GB2015/052802 on Dec. 3, 2015.

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10000460B2 (en) * 2014-09-26 2018-06-19 Thomas Swan & Co. Ltd Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst

Also Published As

Publication number Publication date
WO2016046575A1 (en) 2016-03-31
CN106414419A (zh) 2017-02-15
US10000460B2 (en) 2018-06-19
CN106414419B (zh) 2020-04-17
EP3134203B1 (en) 2018-04-04
US20170029394A1 (en) 2017-02-02
GB2534629B (en) 2017-12-13
GB2534629A (en) 2016-08-03
GB201517051D0 (en) 2015-11-11
GB201417035D0 (en) 2014-11-12
EP3134203A1 (en) 2017-03-01
US20170197929A1 (en) 2017-07-13

Similar Documents

Publication Publication Date Title
US10000460B2 (en) Chelate-controlled diastereoselective hydrogenation with heterogeneous catalyst
Vidal et al. Chemicals from biomass: chemoselective reductive amination of ethyl levulinate with amines
EP3235801B1 (en) Carboxylic acid ester production method
CN105777488B (zh) 一种催化制备脂肪醇的方法
Li et al. Cascade strategy for atmospheric pressure CO2 fixation to cyclic carbonates via silver sulfadiazine and Et4NBr synergistic catalysis
Upadhyay et al. Ruthenium nanoparticle-intercalated montmorillonite clay for solvent-free alkene hydrogenation reaction
JP6222619B2 (ja) ポリエーテルジオール及びその製造方法
JPWO2014034879A1 (ja) 銅系触媒前駆体およびその製造方法並びに水素化方法
Jiang et al. Photo-induced energy transfer relay of N-heterocyclic carbene catalysis: an asymmetric α-fluorination/isomerization cascade
CN109485621A (zh) 一种生产伽马戊内酯的方法
Jiang et al. Etherification of Ferrocenyl Alcohol by Highly‐efficient Ytterbium Triflate
Doohan et al. A comparative analysis of the functionalisation of unactivated cycloalkanes using alkynes and either sunlight or a photochemical reactor
MX2012014881A (es) Un catalizador de oxido mezclado y un proceso para la produccion de acidos o esteres carboxilicos etilenicamente no saturados.
Tian et al. Low-Temperature Production of Glyceric Acid from Biomass-Based Sugar via the Cooperative Roles of MgO and NaBF4
JP4979230B2 (ja) テトラヒドロピラン化合物の製造方法及び該製造方法で製造されるテトラヒドロピラン化合物
KR102019042B1 (ko) 알킬 3-알콕시프로피오네이트의 제조방법
JP2014513053A (ja) フッ化ジオールの製造方法
Bayguzina et al. Synthesis of alkyl biphenyl-4-carboxylates by reaction of biphenyl with carbon tetrachloride and alcohols in the presence of Fe (CO).
EP3619186B1 (en) Process for the production of semifluorinated alkanes
JP5478097B2 (ja) ２−アルキル−２−シクロアルケン−１−オンの製造方法
Nikoshvili et al. Pd Nanoparticles Incorporated in Highly Porous Hyper-Crosslinked Polystyrene as Effective Catalysts of Suzuki Cross-Coupling.
Cao et al. Kinetic Modeling of Erythritol Deoxydehydration and Consecutive Hydrogenation over the ReO x-Pd/CeO2 Catalyst
JP2016013986A (ja) ポリエーテルポリオール及びその製造方法
JPWO2018180610A1 (ja) α，α−ジフルオロアセトアルデヒドヘミアセタールの製造方法
JP7208542B2 (ja) フルオロアルカン化合物の製造方法

Legal Events

Date Code Title Description
AS Assignment

Owner name: THOMAS SWAN & CO. LTD, GREAT BRITAIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DUNN, DAVID;SUTTON, HOWARD WINSTON TYRRELL;DALY, JOHN ING CHUAN;AND OTHERS;SIGNING DATES FROM 20161019 TO 20161020;REEL/FRAME:040197/0622

STCF Information on status: patent grant

Free format text: PATENTED CASE

MAFP Maintenance fee payment

Free format text: PAYMENT OF MAINTENANCE FEE, 4TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1551); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

Year of fee payment: 4